Hippocampal sclerosis in senile dementia of the neurofibrillary tangle type

Senile dementia of the neurofibrillary tangle type (SD-NFT) is a subset of dementia in elderly individuals. Recent studies have reported a correlation between hippocampal sclerosis (HS) and aging. This study aimed to investigate the relationship between HS and SD-NFT.

We conducted a clinical and neuropathological review of Japanese patients diagnosed with SD-NFT. Hematoxylin-eosin and Klüver-Barrera staining, Gallyas silver impregnation, and immunohistochemistry were employed. Pathological assessments focused on identifying HS, neuritic plaques, and phosphorylated transactive response DNA-binding protein 43 (p-TDP-43)-positive inclusions. Additionally, we quantified the densities of neurofibrillary tangles (NFTs) and ghost tangles (GTs) within the hippocampal CA1 region.

Nine patients met the criteria for SD-NFT from the patients who underwent consecutive autopsies from 1994 to 2022 at our institute. The mean ages at onset and death were 84.0 ± 6.8 years (range, 76-94 years) and 91.0 ± 7.0 years (range, 79-101 years), respectively. The mean dementia duration was 7.0 ± 4.0 years (range, 1-13 years). All patients exhibited memory loss although none were diagnosed with SD-NFT during their lifetime. The mean brain weight was 1124.2 ± 132.1 g (range, 980-1390 g). Three patients displayed HS. NFT and GT densities were significantly higher in patients with HS than in those without HS. No significant correlation was found between HS and p-TDP-43 inclusions in the medial temporal lobe.

In SD-NFT, NFTs are more strongly associated with HS. This finding enhances our understanding of the pathological underpinnings of HS in SD-NFT.